German Pat. No. 1,197,460 discloses a process for the preparation of very pure salts of ampicillin which comprises reacting crude ampicillin with a trialkylamine in an organic solvent to form the corresponding ammonium salt of ampiillin and, after separating impurities, precipitating the alkali metal salt of ampicillin by further reaction with an alkali metal salt of a carboxylic acid.
The said German Patent teaches, inter alia, that aqueous solutions of salts of ampicillin, which may be prepared by dissolving ampicillin in an aqueous solution of the calculated amount of sodium bicarbonate for example, are not very stable; upon evaporation of such solutions, even under the most gentle conditions such as in the rotary evaporator or by freeze-drying, about half of the ampicillin in the recovered salt has been destroyed. Therefore, it does not appear to be possible to isolate salts of ampicillin from aqueous solutions without significant decomposition of the ampicillin.
The belief that salts of ampicillin cannot be isolated from aqueous solutions without substantial decomposition of the ampicillin has heretofore to our knowledge never been put in doubt. Accordingly, subsequent prior publications such as German Offenlegungsschrift Nos. 1,670,111, 1,670, 191, 1,795,129 and 1,903,388 always disclose the same basic process, that is, the double decomposition of ammonium salts of ampicillin in organic solvents, as the only useful method for the preparation of alkali metal salts of ampicillin.